China
Africa
Explore chapters and articles related to this topic
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Daratumumab (Darzalex™) is a first-in-class humanized IgG1 antibody targeting the CD38 epitope. It is used for the treatment of multiple myeloma and non-Hodgkin’s lymphomas. CD38 is expressed on multiple immune system cell types, and is highly expressed in hematological malignancies, including multiple myeloma. Daratumumab was approved in the USA in 2015 for patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent. The US FDA granted breakthrough therapy designation to daratumumab in 2013, and approval in 2015 was made via the agency’s accelerated approval program. In 2018, the FDA expanded the approval of daratumumab for use in combination with bortezomib, melphalan, and prednisone to include the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.
Multiple Myeloma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Grade III–IV neuropathy with bortezomib has been significantly reduced by switching from intravenous to subcutaneous injection and a weekly schedule without reduced efficacy. Other side effects with bortezomib include gastrointestinal toxicity, thrombocytopenia, herpes zoster, and hypotension. Both thalidomide and lenalidomide are prothrombotic, and all patients must be assessed for thrombotic risk with a view to starting on appropriate prophylaxis which is typically either prophylactic-dose low-molecular-weight heparin or aspirin. Thalidomide also causes constipation, neuropathy, and somnolence. Lenalidomide although derived from thalidomide does not cause these side effects but does cause fatigue and myelosuppression and requires dose reduction in renal failure. With daratumumab the most common side effect is typically a mild infusional toxicity with the first dose.
Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Elotuzumab and daratumumab are two relatively new mAbs approved by the FDA in 2015 for treatment of patients with relapsed or refractory MM. Elotuzumab targets directly the glycoprotein receptor SLAMF7 (Signalling Lymphocyte Activation Molecule Family Member 7) that is overexpressed on the surface of myeloma and NK cells but is not found on normal cells. It exerts a dual effect in that it activates NK cells directly and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC) by recruiting activated NK cells on MM cells (Lonial et al., 2015). Daratumumab is a human anti-CD38 IgG1 (κ subclass) antibody. It targets the protein CD38 (also an enzyme that catalyzes the metabolism of cyclic adenosine diphosphate ribose and nicotinic acid adenine dinucleotide phosphate) that is overexpressed on multiple myeloma cells and also expressed on many types of immune cells. Its antimyeloma effect mainly relies on its prominent ADCC and complement-dependent cytotoxicity (CDC) activities (Phipps et al., 2015). This topic is discussed in more detail in Section 21.2.3.4.3.
Long-term storage protocol of reagent red blood cells treated with 0.01M dithiothreitol (DTT) for pre-transfusion testing of patients receiving anti-CD38 therapy, daratumumab
Published in Hematology, 2023
Yuyuan Li, Chengyao Li, Ling Zhang, Jiao Li, Qixin Li, Haining Ouyang, Jiaona Luo, Linrui Zhu, Kui Cai
In conclusion, daratumumab is increasingly being used in the therapy of patients with relapsed and refractory multiple myeloma [18]. This study provides transfusion departments and blood banks with a storage protocol of reagent RBCs for the pre-transfusion examinations of patients treated with daratumumab. This protocol enables stable storage of DTT-treated reagent RBCs for 18 days without affecting the detection of most antibodies, which is significantly better than other current treatment methods. In clinical applications, it can guarantee that patients receive safe, timely, and effective blood transfusion treatment. And as alloantibodies can be rapidly detected, current expert recommendations such as phenotyping and genotyping of patients’ RBCs prior to the daratumumab therapy and the provision of phenotype-matching or K-negative RBCs may be unnecessary [6–8, 17]. Hosokawa named his research protocol the ‘Osaka method’, and similarly, our group named the described protocol the ‘Foshan method’.
Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group
Published in Amyloid, 2023
Ashutosh D. Wechalekar, M. Teresa Cibeira, Simon D. Gibbs, Arnaud Jaccard, Shaji Kumar, Giampaolo Merlini, Giovanni Palladini, Vaishali Sanchorawala, Stefan Schönland, Christopher Venner, Mario Boccadoro, Efstathios Kastritis
There are many potential options available for treatment of relapse systemic AL amyloidosis; proteasome inhibitors (PI), monoclonal antibodies (mAb), immunomodulatory therapy (IMIDs), venetoclax, bendamustine, and high dose melphalan with autologous stem cell transplantation (ASCT). The options of patient relapsing or progressing on D-VCD remain unclear. Whilst it is not possible to be prescriptive regarding the optimal sequencing of therapies, the two guiding principles are the depth and duration of initial response, use of a class of agents not previously exposed as well as the limitation imposed by patients’ fitness/frailty and end organ damage. For example, prolonged response with bortezomib based regime (with no neuropathy) would encourage re-treatment with a PI, ideally with a different partner for combination. In patients without prior daratumumab exposure, daratumumab based regime may be favoured. Enrolment in clinical trials is encouraged.
Efficacy of maintenance treatment in patients with multiple myeloma: a systematic review and network meta-analysis
Published in Hematology, 2022
Yongjin Zhi, Shuojing Bao, Jingcheng Mao, Gufan Chai, Jianfeng Zhu, Chengjiang Liu, Xi Chen
Daratumumab is the first-in-class human monoclonal antibody that targets CD38. After January, 2022, since daratumumab was approved as national essential drugs, economic burden was reduced. daratumumab 16 mg/kg intravenously every 4 weeks or every 8 weeks (a reduced frequency compared with standard daratumumab long-term dosing according to patient's tolerability) as maintenance therapy for patients were accepted [17,23]. The main toxicity of daratumumab consists of infusion-related reactions (IRRs); in addition, the CD38 expression of the airway muscle cells partially explains the main symptoms that involve the respiratory tract, with throat irritation, cough [30]. However, treatment discontinuation due to IRRs is uncommon. In clinical practice, to prevent severe respiratory adverse events, standard premedication of daratumumab with steroids, antihistamines, and antipyretics administration is recommended. Switching from an intravenously administered to a subcutaneous therapy to minimize the treatment burden may make prolonged daratumumab therapy more feasible in the community settings [31]. Furthermore, daratumumab does not need dose adjustment in patients with renal impairment. Therefore, daratumumab may be an alternative option for certain patients.